DESCRIPTION: In vertebrates, blood development begins during gastrulation and results from the induction of extraembryonic (ventral) mesoderm to form hematopoietic tissue. Although the precursors that give rise to blood cells are mesodermal in origin, tissue recombination studies with chick embryos suggest that their differentiation depends on inductive factors from the visceral yolk sac. Bone morphogenetic proteins (BMP) are members of the TGF-B family that bind to type I and II serine/threonine kinase receptors. A variety of experimental evidence has shown that BMPs have important roles in embryonic development other than bone formation. For example, BMP-4 has been demonstrated to be important in the induction of extraembryonic hematopoietic mesoderm. Targeted disruption of BMP-4 causes embryonic lethality between days 6.5 and 9.5 of gestation and results in severe defects in mesoderm formation/differentiation, including visceral yolk sac hematopoietic mesoderm. Mice homozygous null for the type I Bmp-2/4 receptor are unable to form mesoderm. BMPs may function in vivo as heterodimers. BMP-7 is expressed in many of the same or adjacent tissues as BMP-4 and BMP-4/BMP-7 heterodimers have been shown to have potent ventralizing activity in Xenopus animal cap assays. This proposal will examine how BMP-4 and related proteins function in the induction of yolk sac hematopoietic mesoderm.